The present invention relates to a new and improved construction of a filtering apparatus for use with at least one analytical instrument. The present invention also relates to a new and improved method of feeding a filtered liquid medium to at least one analytical instrument.
In its more particular aspects, the present invention specifically relates to a new and improved filtering apparatus for fine-filtering a liquid medium such as, for instance, a liquid reagent, a reagent solution, a solvent, a diluent or the like for use with at least one analytical instrument like, for example, at least one particle analyzer and is especially intended for use in the field of automated analyzers.
Particularly in the field of particle analysis it is highly significant whether the employed reagents as such are free of particles or contain only a very small number of particles. The reason therefore is that foreign particles falsify the analysis results in a manner similar to the known manner in which, for example, colored contaminants of solvents falsify the analytical results in colorimetry. When adhering to the example of colorimetric measurements, the colored contamination can be "eliminated" by a correcting reference or compensation measurement without any notable effort, however, when carrying out particle analysis, the problem is different and substantially more complex.
Generally, such particle analysis comprises a true counting process during which the particles are individually detected. Contrary thereto, there is only drawn an indirect conclusion with respect to the concentration or the amount of a compound which is contained in a solution or the like, when utilizing an optical measurement, i.e. a measurement relying upon measuring a statistical average. Furthermore, during particle analysis, there is in general simultaneously also measured the size of the particles in addition to the number of particles so that a measuring operation which measures "en bloc" or bulk properties like, for example, the optical absorption or extinction, cannot be utilized. Thus the particle analysis constitutes a type of measurement which can be associated with spectroscopy and its problems rather than measuring methods which determine the measuring result in a single measuring operation in terms of time. In correspondence therewith, the problems caused by interfering factors which affect the measurement or the measuring result, are of higher complexity and thus much more difficult to eliminate. Therefore, the direct compensation using known methods such as the comparison with a reference could not succeed in the field of particle analysis.
Thus, it is still required to utilize high-purity liquid media such as reagents, reagent solutions, solvents and diluents or the like in order to obtain acceptable "blank counts" for particle analysis. The term "blank count" is the term designating the number and size distribution of a residual amount of foreign particles which can not be eliminated.
In this connection, however, other problems arise which are not directly connected with the actual measuring operation but rather with the operation preceding the actual measurement. The preparation of liquid media such as reagents, nearly or totally free of particles, does not as such constitute a problem and there can be no doubt that products which have been prepared and placed into their containers, in fact, satisfy the requirements of modern and particularly automated particle measuring techniques. However, this situation is basically changed when such liquid media like reagents, reagent solutions, solvents or diluents are handled in greater volumes as required, for example, in automatic analyzers having sufficiently large reservoirs. A further decisive aspect is the following:
The reagents or reagent solutions which are used during particle analysis, are nearly totally made up of the solvent, for example, water which in general comprises well over 90 percent of the total volume. Thus, manufacturers would tend to, for instance, offer and ship vehicle-free pre-mixed compositions, i.e. concentrates which contain only small amounts of solvent, unless there would not exist the problem of properly and ultimately still carrying out quite expensive processing of the concentrate in order to obtain the utilizable liquid medium such as the reagent, reagent solution or the like. These are true limits which restrict the selection of available possibilities.
Generally, a liquid phase is freed from solid materials, specifically particles contained therein by means of filtration. The filtering procedure, however, constitutes a rather slow process which is better suited for a batch operation as compared to a continuous operation. However, whenever a filtering operation is intended to be included in a continuous operation, quite a series of compromises have to be made and one of the main compromises is the significant overdimensioning of the filtering apparatus inclusive of the pump used for the filtering operation. One of the reasons therefore is that, in a continuous process, a filtering location constitutes a bottleneck. This is still true in those cases in which the process constitutes merely a quasi-continuous process comprising a number of discontinuous steps which are carried out at a high repetition rate.
In specific cases of particle analysis, for example, hematology, the capability of detecting progressively smaller particles by the particle analysis gains increasing importance. During cancer therapy or treatment, for instance, for controlling the course of pathological cell disorders, the specific capability or particle analysis in the region of very small or submicron particles would significantly extend existing possibilities. However, there would naturally result correspondingly increased requirements concerning the utilized liquid media such as reagents, reagent solutions, solvents, diluents and the like which then must be freed from such very small or submicron particles. Such particles previously have been considered immeasurably small and their presence would markedly disturb the particle measurement or analysis in this particle size range. Ultimately this may result in the fact that the presently usual ready-to-use liquid media which are supplied, for example, in cubitainers, can no longer be provided in the required quality. Thus the available ready-to-use liquid media merely would be at a pre-stage of the required purity and thus could no longer be used as such.
When intending to introduce into particle analysis the filtering of liquid media such as reagents, reagent solutions, solvents, diluents and the like containing particles in the submicron size range, there would have to be provided a filtering apparatus in conjunction with the particle analyzer, in the first place. Additionally and in the second place, such filtering apparatus would have to be a specific filtering apparatus which would have to be specifically constructed for this purpose and which would have to satisfy the following criteria:
a. At every instant of use, there would have to be present a sufficient amount of the liquid medium such as the reagent, reagent solution, solvent, diluent or the like;
b. This sufficient amount or volume of the liquid medium would have to be freshly filtered at each instant of use in order to eliminate or minimize as far as possible any interim contamination, i.e. this sufficient amount or volume would have to be subject to extremely short storage periods; and
c. The limiting filtering frequency, i.e. the maximum possible filtering rate of the filtering apparatus should be above the limiting frequency of the automatic analyzer, i.e. above the maximum possible throughput of one or more automatic analyzers which are connected to the filtering apparatus. This requirement corresponds to the filtering capacity or power which must be offered by the filtering apparatus.
It will be immediately evident that the aforementioned individual requirements diametrically oppose or counter each other at least in part.